12-48119350-C-T

Variant names:

• chr12-48119350-C-T
• rs886345958
• ENST00000546964.5:n.8C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001354740.1(PFKM):​c.24C>T​(p.Pro8Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000203 in 985,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P8P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: PFKM NM_001354740.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.927
• Publications: 0 publications found

Genes affected

PFKM (HGNC:8877): (phosphofructokinase, muscle) Three phosphofructokinase isozymes exist in humans: muscle, liver and platelet. These isozymes function as subunits of the mammalian tetramer phosphofructokinase, which catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate. Tetramer composition varies depending on tissue type. This gene encodes the muscle-type isozyme. Mutations in this gene have been associated with glycogen storage disease type VII, also known as Tarui disease. Alternatively spliced transcript variants have been described.[provided by RefSeq, Nov 2009]

PFKM Gene-Disease associations (from GenCC):

• glycogen storage disease VII

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=0.927 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354740.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKM	NM_001354740.1		c.24C>T	p.Pro8Pro	synonymous	Exon 1 of 23	NP_001341669.1
	PFKM	NM_001354735.1		c.301+773C>T		intron	N/A	NP_001341664.1	A0A2R8Y891
	PFKM	NM_001354736.1		c.301+773C>T		intron	N/A	NP_001341665.1	A0A2R8Y891

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKM	ENST00000546964.5	TSL:1	n.8C>T		non_coding_transcript_exon	Exon 1 of 22
	PFKM	ENST00000942236.1		c.-65C>T		5_prime_UTR	Exon 1 of 23	ENSP00000612295.1
	PFKM	ENST00000942232.1		c.-65C>T		5_prime_UTR	Exon 1 of 23	ENSP00000612291.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152142 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000120 AC: 1 AN: 832996 Hom.: 0 Cov.: 27 AF XY: 0.00000260 AC XY: 1 AN XY: 384746

African (AFR) AF: 0.0000633 AC: 1 AN: 15786

American (AMR) AF: 0.00 AC: 0 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5152

East Asian (EAS) AF: 0.00 AC: 0 AN: 3638

South Asian (SAS) AF: 0.00 AC: 0 AN: 16458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1624

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 761688

Other (OTH) AF: 0.00 AC: 0 AN: 27312

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152142 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74326

African (AFR) AF: 0.00 AC: 0 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.93
PhyloP100		0.93
PromoterAI		-0.21	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs886345958; hg19: chr12-48513133;